June 28, 2017
Scientists at the UNC Gillings School of Global Public Health have confirmed that an experimental antiviral treatment prevents the development of SARS coronavirus (SARS-CoV) disease in mice. The drug, GS-5734, also inhibits MERS-CoV and multiple other coronaviruses (CoV), suggesting that the treatment may inhibit all CoV.
To date, there are no approved therapies to treat any kind of CoV infection. GS-5734 is being developed through a unique public-private partnership between investigators at the University of North Carolina, Vanderbilt University’s School of Medicine and Gilead Sciences, Inc.
The full findings are presented in an article titled, “Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses,” which was published online June 28 by Science Translational Medicine.
The studies of GS-5734 were led by Timothy Sheahan, PhD, research assistant professor, and Amy Sims, PhD, research associate professor, both in the Department of Epidemiology at UNC’s Gillings School. Sheahan and Sims worked with colleagues to test a small-molecule inhibitor – one that already has demonstrated some success against the Ebola virus – as a potential agent in the fight against coronavirus outbreaks.
Watch a short video summarizing these research findings.
Coronaviruses are of special concern to public health practitioners because they can jump from animals into the human population. As witnessed in the SARS and MERS outbreaks of the past two decades, these unpredictable jumps can have devastating effects.
MERS-CoV continues to cause sporadic outbreaks in the Kingdom of Saudi Arabia, and air travel has spread the virus from that origin point to 27 countries including South Korea, which saw almost 200 cases in 2015. In a hospital setting, four in ten people who contract MERS-CoV die from the infection. The actual disease burden remains unclear, however, as seroprevalence studies suggest that ~45,000 people have been infected by MERS-CoV in the Kingdom of Saudi Arabia and parts of eastern Africa.
GS-5734, however, offers hope. The drug was effective against multiple types of coronaviruses in cell cultures and also inhibited SARS-CoV in a mouse model.
“We tested this drug against multiple genetically distinct coronaviruses and it worked great against them all,” said Sheahan, a co-lead author. “The results make us optimistic that this drug could not only be of immediate use in clinical trials for patients with MERS-CoV, but also could be used for any new coronavirus that emerges in the future.”
With viruses similar to SARS- and MERS-CoV circulating in wild animals in nature, there is constant potential for the appearance of a novel virus.
“Emerging CoV represent a significant and ongoing global health threat,” stated Ralph Baric, PhD, a Gillings School professor of epidemiology and senior author of the manuscript. “For the first time, our studies are providing potent treatment options designed not only to protect individuals from life-threatening coronavirus infections but also to block transmission patterns in high-risk settings.”
GS-5734 is the first antiviral drug identified as both highly active and broadly inhibitory for all coronaviruses tested to date. Ongoing studies are aimed at determining whether its use could lead to the generation of drug-resistant virus strains.
In the near future, investigators will accumulate the additional data needed to launch a human clinical trial of the drug in CoV-infected patients. Given the diverse spectrum of coronaviruses that GS-5734 seems to counter, it could then be deployed to prevent the spread of a future outbreak, regardless of the specific virus that jumps over.
As the drug also is effective against Ebola virus, Gilead Sciences, Inc. currently is conducting clinical development with the goal of treating that disease.
“Our integrated partnership with Gilead Sciences, Inc. has led to new discoveries and treatment options for humans infected with a range of novel emerging pathogens,” said co-lead author Sims. “This research provides us with a template for improved global health.”
Other co-authors from the Gillings School include Rachel Graham, PhD, research assistant professor, Vineet Menachery, PhD, postdoctoral scholar, Lisa Gralinski, PhD, research assistant professor, and Sarah Leist, PhD, postdoctoral scholar, all members of Baric’s lab housed within the Department of Epidemiology.